systems networks and cancer
DESCRIPTION
Systems Networks and Cancer. Sharmila Bapat, Ph.D National Centre for Cell Science, Pune, India [email protected]. Bifx Africa-India Joint Virtual Conference 2011. Basic Life Processes. Environment. Individuals. Epigenetic Regulation. Genetic Composition. Homeostasis. Tissues. - PowerPoint PPT PresentationTRANSCRIPT
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Systems Networks and Cancer Sharmila Bapat, Ph.D National Centre for Cell Science, Pune, [email protected] Africa-India Joint Virtual Conference 2011
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EnvironmentMolecular Pathways & NetworksCellsTissuesIndividualsBasic Life ProcessesHomeostasisGenetic CompositionEpigenetic RegulationBifx Africa-India Joint Virtual Conference 2011
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Digitalization of the human genome ChromatinChromosomesGenes (DNA)RNAProteins
NetworksCellsTissuesIndividualsEnvironmentBifx Africa-India Joint Virtual Conference 2011
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Imbalance in such profiles that constitute networks leads to aberrant states
such as cancer
in which cell, tissue and functioning are compromised.Bifx Africa-India Joint Virtual Conference 2011
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It thus becomes pertinent to question cancer as an aberrant state defined
by disrupted networks in the transformed cell / tissue
i.e.
Resolve the transformed state as a function of systems networks rather
than address it on a reductionist level as being driven by a single geneBifx Africa-India Joint Virtual Conference 2011
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Systems Biology
Hypothesis-driven
Global data acquisition
Integrate data from different platforms/diff types of data
Delineate biological network dynamics
Formulate models that can be validatedApplying the principles of systems biologyBifx Africa-India Joint Virtual Conference 2011
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An example in point studied recently in our lab is that of
the identification of a gene signature associated with
serous ovarian adenocarcinoma Bifx Africa-India Joint Virtual Conference 2011
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Serous ovarian adenocarcinoma is one of the most aggressive
Gynecological cancers and is associated with a
very poor prognosis for most patients
It is often termed as Silent Killer because of lack of early symptoms of
disease and rapid progression to a metastatic stage Bifx Africa-India Joint Virtual Conference 2011
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Poor correlation in biomarkers identified betweenprevious studies
- Limited sample size - Limited normal tissue primary Vs.metastases - Discrepancy across microarray platforms - Limited validationIntegrative Approaches for the identification and assessment of Cancer BiomarkersBifx Africa-India Joint Virtual Conference 2011
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1. A4 in vitro model transformation systemDifferential Gene Expression Databases for serous ovarian carcinomas 2. IST - In Silico Transcriptomics3. TCGA -The Cancer Genome AtlasIdentification of a SeOvCa gene signature based on transcriptional profilingBifx Africa-India Joint Virtual Conference 2011
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Analytical Pipeline
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SeOvCa gene signatureCDCA4EXO1LAMA5MALMCM2MESTMMP9RRM2SLC39A4SOX17SYNCRIPTM7SF2TNNT1DAB2DIXDC1EFEMP1FBN1GNB5HNMTKLF2LHFPLRRC17PAPSS2PROS1PTGISRNASE4SGK1SMARCA2ATAD2Downregulated genesBCAT1Bifx Africa-India Joint Virtual Conference 2011
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In silico validation with the database Prognoscan-1+2Bifx Africa-India Joint Virtual Conference 2011
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Algorithm for the Reconstruction of Accurate Cellular NetworksSystems Networks Analysis Applying ARACNe 30 SeOvCa signature genes were considered as nodes around which interactions were predicted as individual or interacting hubs.
The MI (Mututal Information) was fixed at 0.20
DPI (Data Processing Inequality) was set at 0.10. Bifx Africa-India Joint Virtual Conference 2011
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Node - Interacting Genes Network (27-781) Stand-alone NodesSocial NodesBifx Africa-India Joint Virtual Conference 2011
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Node - Linker - Node Interactions (23 nodes 95 linkers)Bifx Africa-India Joint Virtual Conference 2011
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Components of the Interface Network (20 nodes 9 linkers)Bifx Africa-India Joint Virtual Conference 2011
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Chromosomal location analyses of the networkNode-gene same chromosome location
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Predictions of copy no. amplifications6q12 - 6q16.16q218q24.320q11.2-20q13.3SYNCRIPATAD2SLC39A4LAMA5Bifx Africa-India Joint Virtual Conference 2011
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6q21 /8q24.320qValidation - FISHBifx Africa-India Joint Virtual Conference 2011
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MALMESTEFEMP1PAPSS2PTGISFBN1ELELELELELH3K9H3K27H3K4INPUTAb CTRLPTGISMALMEST-4723-4673-4592-4542-3523-3473369413499455-122-930-866-405-349-251-171-107-6390134A2A1A2A1PAPSS2EFEMP1FBN1-3003-2951-203-159-77-1522-1244-1478-1200-1122-1077-233-189A1A1A1A1HypomethylationNo change in methylation K4K27K4-K9K4-K27K9-K27K4-K9-K27TSSDOWNEpigenetic Regulation of some SeOvCa genesBifx Africa-India Joint Virtual Conference 2011
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Protein Interaction Networks (PINA)Bifx Africa-India Joint Virtual Conference 2011
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Overlap of ARACNe and PINA NetworksBifx Africa-India Joint Virtual Conference 2011
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c-MYCp53Rb1Gene and Protein NetworksBifx Africa-India Joint Virtual Conference 2011
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Identification of functional modules in serous ovarian adenocarcinomaBifx Africa-India Joint Virtual Conference 2011
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Sharmila A. Bapat, Anagha Krishnan, Avinash D. Ghanate, Anjali P. Kusumbeand Rajkumar S. Kalra -
Gene Expression: Protein Interaction Systems Network Modeling Identifies
Transformation-Associated Molecules and Pathways in Ovarian Cancer
Cancer Research 70(12); 480919 2010References for this presentation cited in the following publication
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AcknowledgementsCollaborators
Dr. C.B.Koppiker, Jehangir Hospital, PuneDr. Matthias Nees, VTT, Turku, FinlandDr. Renu Wadhwa, AIST JapanDr. Sunil Kaul, AIST JapanFunding
Department of Biotechnology, Ministry of Science & Technology, Govt. of IndiaMr. Avinash MaliMs. Anjali KusumbeMr. Rajkumar Kalra Mr. Brijesh KumarMr. Anand Kamal SinghMs. Rutika NaikMs. Rohini KshirsagarMs. Tejaswini DeshpandeMr. Swapnil KambleMr. Nilesh GardeDr. Nicholas BerryDr. Nawneet KurreyDr. Neeti SharmaMs. Swati JalgaonkarMs. Shweta JadhavMs. Nimisha SinghMr. Avinash GhanateMs. Anagha KrishnanMr. Prasad ChaskarMr. Mihir MetkarMs. Divya RamalingamMr. Alok JoglekarAlumniResearch group@NCCS